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The CA1 region of the hippocampus is one of the most studied regions of the rodent brain, thought to play an important role in cognitive functions such as memory and spatial navigation. Despite a wealth of experimental data on its structure and function, it has been challenging to integrate information obtained from diverse experimental approaches. To address this challenge, we present a community-based, full-scale in silico model of the rat CA1 that integrates a broad range of experimental data, from synapse to network, including the reconstruction of its principal afferents, the Schaffer collaterals, and a model of the effects that acetylcholine has on the system. We tested and validated each model component and the final network model, and made input data, assumptions, and strategies explicit and transparent. The unique flexibility of the model allows scientists to potentially address a range of scientific questions. In this article, we describe the methods used to set up simulations to reproduce in vitro and in vivo experiments. Among several applications in the article, we focus on theta rhythm, a prominent hippocampal oscillation associated with various behavioral correlates and use our computer model to reproduce experimental findings. Finally, we make data, code, and model available through the hippocampushub.eu portal, which also provides an extensive set of analyses of the model and a user-friendly interface to facilitate adoption and usage. This community-based model represents a valuable tool for integrating diverse experimental data and provides a foundation for further research into the complex workings of the hippocampal CA1 region. Integrating data from different experimental approaches into one model is challenging. This study presents a community-based, full-scale in silico model of the rat hippocampal CA1 region that integrates diverse experimental data from synapse to network. [ABSTRACT FROM AUTHOR]

Endogenous shifts of spatial attention toward an upcoming stimulus are associated with improvements in behavioral responses to the stimulus, preparatory retinotopic shifts in alpha power, and changes in ERPs. Although attentional modulation of several early sensory ERPs is well established, there is still debate about under what circumstances attention affects the earliest cortical visual evoked response—the C1 ERP component—which is putatively generated from afferent input into primary visual cortex. Moreover, the effects of spatial attention on the recently discovered ERP signature of evidence accumulation—the central parietal positivity (CPP)—have not been fully characterized. The present study assessed the effect of spatial attention on the C1 and CPP components through a spatially cued contrast discrimination task using stimuli that were specifically designed to produce large-amplitude C1 responses and that varied in sensory evidence strength to characterize the CPP. Participants responded according to which of two checkerboard stimuli had greater contrast following an 80% valid cue toward the upper or lower visual field. Prestimulus alpha power changed topographically based on the cue, suggesting participants shifted attention to prepare for the upcoming stimuli. Despite these attentional shifts in alpha power and the fact that the stimuli reliably elicited C1 responses several times greater than many prior studies, there was no evidence of an attention effect on the C1. The CPP, however, showed a clear increase in build-up rate on valid trials. Our findings suggest that endogenous attention may not affect the early C1 ERP component but may improve behavior at a decision stage, as reflected in brain signals related to evidence accumulation (the CPP). [ABSTRACT FROM AUTHOR]

The article titled "A Hundred Faces for a Unique Disorder: Hereditary Spastic Paraplegia" provides an overview of Hereditary Spastic Paraplegia (HSP), a group of inherited neurodegenerative disorders characterized by lesions of the pyramidal tract. The disorder presents with progressive lower limb spasticity and weakness, and exhibits wide clinical and genetic variability. The article discusses the genetic causes of HSP, including various inheritance patterns and the involvement of over 80 genes. It also describes the clinical presentation of HSP, highlighting the differences based on age of onset and the presence of additional neurological or non-neurological features. This document provides information on hereditary spastic paraplegia (HSP), a rare and diverse clinical disorder characterized by progressive weakness and spasticity in the lower limbs. The diagnosis of HSP is based on symptoms, family history, and genetic analysis. Treatment aims to manage symptoms and prevent complications, but there is currently no cure for HSP. The prognosis varies, with some individuals experiencing severe disability and others having a normal life expectancy. Early diagnosis and treatment can help reduce symptoms associated with HSP. [Extracted from the article]

Numerous studies have underscored the close relationship between the auditory and vibrotactile modality. For instance, in the peripheral structures of both modalities, afferent nerve fibers synchronize their activity to the external sensory stimulus, thereby providing a temporal code linked to pitch processing. The Frequency Following Response is a neurological measure that captures this phase locking activity in response to auditory stimuli. In our study, we investigated whether this neural signal is influenced by the simultaneous presentation of a vibrotactile stimulus. Accordingly, our findings revealed a significant increase in phase locking to the fundamental frequency of a speech stimulus, while no such effects were observed at harmonic frequencies. Since phase locking to the fundamental frequency has been associated with pitch perceptual capabilities, our results suggests that audio-tactile stimulation might improve pitch perception in human subjects. [ABSTRACT FROM AUTHOR]

Memory consolidation involves repeated replay of new information by the hippocampus, which transfers memories to the neocortex for long-term storage. This occurs mainly during slow wave sleep, a phase characterized in the cortex by low cholinergic tone and low afferent input. High cholinergic tone has been shown to hamper memory consolidation, probably mediated by reduced network excitability (the ease of activity propagation in a network). We used cortical neuronal networks on multi electrode arrays to investigate whether low background input contributes to memory consolidation. Networks received focal electrical stimuli to memorize, with or without background afferent input (global optogenetic stimulation). Background stimulation hampered memory formation and consolidation, confirming the importance of low background input. Moreover, it lowered network excitability, similar to high cholinergic tone. These findings suggest that high network excitability is a critical feature of slow wave sleep that facilitates memory consolidation. [ABSTRACT FROM AUTHOR]

The absence of a comprehensive understanding of the neural basis of spontaneous pain limits the development of therapeutic strategies targeting this primary complaint of patients with chronic pain. Here we report a distinct neuronal ensemble within the prelimbic cortex which processes signals related to spontaneous pain in rats with chronic inflammatory pain. This neuronal ensemble specifically encodes spontaneous pain-related behaviors, independently of other locomotive and evoked behaviors. Activation of this neuronal ensemble elicits marked spontaneous pain-like behaviors and enhances nociceptive responses, whereas prolonged silencing of its activities alleviates spontaneous pain and promotes overall recovery from inflammatory pain. Notably, afferents from the primary somatosensory cortex and infralimbic cortex bidirectionally modulate the activities of the spontaneous pain-responsive prelimbic cortex neuronal ensemble and pain behaviors. These findings reveal the cortical basis of spontaneous pain at the neuronal level, highlighting a distinct neuronal ensemble within the prelimbic cortex and its associated pain-regulatory brain networks. Neural mechanisms underlying spontaneous pain are not fully understood. Here authors identify a unique neuronal ensemble in the PL of rats with chronic inflammation, encoding spontaneous pain independently. Activating this ensemble triggers pain-like behaviors, while inhibiting it alleviates pain and accelerates recovery. [ABSTRACT FROM AUTHOR]

Research has shown that talkers reliably coordinate the timing of articulator movements across variation in production rate and syllable stress, and that this precision of inter-articulator timing instantiates phonetic structure in the resulting acoustic signal. We here tested the hypothesis that immediate auditory feedback helps regulate that consistent articulatory timing control. Talkers with normal hearing recorded 480 /tV#Cat/ utterances using electromagnetic articulography, with alternative V (/ɑ/-/ɛ/) and C (/t/-/d/), across variation in production rate (fast-normal) and stress (first syllable stressed-unstressed). Utterances were split between two listening conditions: unmasked and masked. To quantify the effect of immediate auditory feedback on the coordination between the jaw and tongue-tip, the timing of tongue-tip raising onset for C, relative to the jaw opening-closing cycle for V, was obtained in each listening condition. Across both listening conditions, any manipulation that shortened the jaw opening-closing cycle reduced the latency of tongue-tip movement onset, relative to the onset of jaw opening. Moreover, tongue-tip latencies were strongly affiliated with utterance type. During auditory masking, however, tongue-tip latencies were less strongly affiliated with utterance type, demonstrating that talkers use afferent auditory signals in real-time to regulate the precision of inter-articulator timing in service to phonetic structure. [ABSTRACT FROM AUTHOR]

The 46th meeting of the Upper Midwest Neuro-Ophthalmology Group (UMNOG), held on July 26, 2024, and hosted by Northwestern University at Chicago, brought together a group of neuro-ophthalmologists, researchers, and trainees. This conference served as a forum for presenting research findings, illustrating challenging cases in clinical practice, and discussing them from an expert viewpoint. Key topics included visual outcomes following the treatment of various optic neuropathies, and advancements in diagnostic techniques, including the integration of machine learning. Case demonstrations covered a wide range of afferent and efferent neuro-ophthalmological conditions, primarily related to systemic illnesses and novel treatments. The proceedings aimed to disseminate valuable knowledge and foster further research, offering comprehensive insights into the discussion held during the meeting. [ABSTRACT FROM AUTHOR]

In the mammalian somatosensory system, polymodality is defined as the competence of some neurons to respond to multiple forms of energy (e.g., mechanical and thermal). This ability is thought to be an exclusive property of nociceptive neurons (polymodal C-fiber nociceptors) and one of the pillars of nociceptive peripheral plasticity. The current study uncovered a completely different neuronal sub-population with polymodal capabilities on the opposite mechanical modality spectrum (tactile). We have observed that several tactile afferents (1/5) can respond to cold in non-nociceptive ranges. These cells' mechanical thresholds and electrical properties are similar to any low-threshold mechano-receptors (LT), conducting in a broad range of velocities (Aδ to Aβ), lacking CGRP and TRPM8 receptors. Due to its density, cold-response range, speed, and response to injury (or lack thereof), we speculate on its role in controlling reflexive behaviors (wound liking and rubbing) and modulation of nociceptive spinal cord integration. Further studies are required to understand the mechanisms behind this neuron's polymodality, central architecture, and impact on pain perception. [ABSTRACT FROM AUTHOR]

Inhibitory circuits in the mammalian olfactory bulb (OB) dynamically reformat olfactory information as it propagates from peripheral receptors to downstream cortex. To gain mechanistic insight into how specific OB interneuron types support this sensory processing, we examine unitary synaptic interactions between excitatory mitral and tufted cells (MTCs), the OB projection neurons, and a conserved population of anaxonic external plexiform layer interneurons (EPL-INs) using pair and quartet whole-cell recordings in acute mouse brain slices. Physiological, morphological, neurochemical, and synaptic analyses divide EPL-INs into distinct subtypes and reveal that parvalbumin-expressing fast-spiking EPL-INs (FSIs) perisomatically innervate MTCs with release-competent dendrites and synaptically detonate to mediate fast, short-latency recurrent and lateral inhibition. Sparse MTC synchronization supralinearly increases this high-fidelity inhibition, while sensory afferent activation combined with single-cell silencing reveals that individual FSIs account for a substantial fraction of total network-driven MTC lateral inhibition. OB output is thus powerfully shaped by detonation-driven high-fidelity perisomatic inhibition. Inhibitory circuits in the mammalian olfactory bulb shape information as it propagates from peripheral receptors to the downstream cortex. This study reveals that fast-spiking interneurons perisomatically inhibit projection neurons in the mammalian olfactory bulb via synaptic detonation. [ABSTRACT FROM AUTHOR]

The emulation of tactile sensory nerves to achieve advanced sensory functions in robotics with artificial intelligence is of great interest. However, such devices remain bulky and lack reliable competence to functionalize further synaptic devices with proprioceptive feedback. Here, we report an artificial organic afferent nerve with low operating bias (−0.6 V) achieved by integrating a pressure-activated organic electrochemical synaptic transistor and artificial mechanoreceptors. The dendritic integration function for neurorobotics is achieved to perceive directional movement of object, further reducing the control complexity by exploiting the distributed and parallel networks. An intelligent robot assembled with artificial afferent nerve, coupled with a closed-loop feedback program is demonstrated to rapidly implement slip recognition and prevention actions upon occurrence of object slippage. The spatiotemporal features of tactile patterns are well differentiated with a high recognition accuracy after processing spike-encoded signals with deep learning model. This work represents a breakthrough in mimicking synaptic behaviors, which is essential for next-generation intelligent neurorobotics and low-power biomimetic electronics. Intelligent artificial tactile system for neurorobotics remains challenging. Here, Chen et al. developed an artificial organic afferent nerve to implement slip recognition and prevention actions by learning the real-time spatial information of directional touch. [ABSTRACT FROM AUTHOR]

Although the introduction of drugs targeting calcitonin gene-related peptide (CGRP) revolutionized migraine treatment, still a substantial proportion of migraine patients do not respond satisfactorily to such a treatment, and new therapeutic targets are needed. Therefore, molecular studies on migraine pathogenesis are justified. Oxidative stress is implicated in migraine pathogenesis, as many migraine triggers are related to the production of reactive oxygen and nitrogen species (RONS). Migraine has been proposed as a superior mechanism of the brain to face oxidative stress resulting from energetic imbalance. However, the precise mechanism behind the link between migraine and oxidative stress is not known. Nociceptive primary afferent nerve fiber endings express ion channel receptors that change harmful stimuli into electric pain signals. Transient receptor potential cation channel subfamily A member 1 (TRPA1) is an ion channel that can be activated by oxidative stress products and stimulate the release of CGRP from nerve endings. It is a transmembrane protein with ankyrin repeats and conserved cysteines in its N-terminus embedded in the cytosol. TRPA1 may be a central element of the signaling pathway from oxidative stress and NO production to CGRP release, which may play a critical role in headache induction. In this narrative review, we present information on the role of oxidative stress in migraine pathogenesis and provide arguments that TRPA1 may be "a missing link" between oxidative stress and migraine and therefore a druggable target in this disease. [ABSTRACT FROM AUTHOR]

Electrical stimulation is a key tool in neuroscience, both in brain mapping studies and in many therapeutic applications such as cochlear, vestibular, and retinal neural implants. Due to safety considerations, stimulation is restricted to short biphasic pulses. Despite decades of research and development, neural implants lead to varying restoration of function in patients. In this study, we use computational modeling to provide an explanation for how pulsatile stimulation affects axonal channels and therefore leads to variability in restoration of neural responses. The phenomenological explanation is transformed into equations that predict induced firing rate as a function of pulse rate, pulse amplitude, and spontaneous firing rate. We show that these equations predict simulated responses to pulsatile stimulation with a variety of parameters as well as several features of experimentally recorded primate vestibular afferent responses to pulsatile stimulation. We then discuss the implications of these effects for improving clinical stimulation paradigms and electrical stimulation-based experiments. Pulsatile electrical stimulation is a common neuromodulation method, yet its effect on single neuron firing remains unclear. Here the authors show that pulses have multiple unintended but predictable effects on firing and discuss how they may be corrected when designing future neurotechnologies. [ABSTRACT FROM AUTHOR]

Introduction: Hearing decline stands as the most prevalent single sensory deficit associated with the aging process. Giving compelling evidence suggesting a protective effect associated with the efferent auditory system, the goal of our study was to characterize the age-related changes in the number of efferent medial olivocochlear (MOC) synapses regulating outer hair cell (OHC) activity compared with the number of afferent inner hair cell ribbon synapses in CBA/J mice over their lifespan. Methods: Organs of Corti of 3-month-old CBA/J mice were compared with mice aged between 10 and 20 months, grouped at 2-month intervals. For each animal, one ear was used to characterize the synapses between the efferent MOC fibers and the outer hair cells (OHCs), while the contralateral ear was used to analyze the ribbon synapses between inner hair cells (IHCs) and type I afferent nerve fibers of spiral ganglion neurons (SGNs). Each cochlea was separated in apical, middle, and basal turns, respectively. Results: The first significant age-related decline in afferent IHC-SGN ribbon synapses was observed in the basal cochlear turn at 14 months, the middle turn at 16 months, and the apical turn at 18 months of age. In contrast, efferent MOCOHC synapses in CBA/J mice exhibited a less pronounced loss due to aging which only became significant in the basal and middle turns of the cochlea by 20 months of age. Discussion: This study illustrates an age-related reduction on efferent MOC innervation of OHCs in CBA/J mice starting at 20 months of age. Our findings indicate that the morphological decline of efferent MOC-OHC synapses due to aging occurs notably later than the decline observed in afferent IHC-SGN ribbon synapses. [ABSTRACT FROM AUTHOR]

A non-invasive and non-pharmacological approach is evaluated for the proprioceptive and postural improvement of PD subjects. The authors evaluated the effectiveness of a class I medical device according to EU regulation 745/2017 designed to develop the mechanism of action based on the modulation of action potentials, which occurs in prevalent pathways of the afferent peripheral nervous system efferent in subjects with spasticity. The present observational study, structured in a double-blind randomized manner, therefore, had the main aim of evaluating the ability of the device to improve on the motor and proprioceptive function of PD patients. This study was based on the instrumented gait analysis performed according to the Timed Up and Go (TUG) test procedure, as well as using a fall risk assessment in accordance with the Berg Balance Scale (BBS) procedures. This study involved 25 participants in the active group (no placebo) and 25 in the non-active group (placebo), the latter to whom non-functional devices were applied, but in every respect identical to the functional devices applied to the 25 patients in the no placebo group. Data analysis was conducted using statistical methodologies for statistics, the statistical significance of the results for the observed samples and the interdependence between the measured variables. The study of the mechanism of action based on the remodulation of action potentials was preliminary conducted through numerical modeling of the Hodgkin–Huxley axon, modified by introducing the influence of the capacitive device applied in clinical tests into the validated model to target the dielectric properties of materials constituting the passive sensor. The use of the neuromodulation device promises observable improvements in motor function among PD patients, including increased limb mobility and greater postural stability. [ABSTRACT FROM AUTHOR]

The thalamic reticular nucleus (TRN) serves as an important node between the thalamus and neocortex, regulating thalamocortical rhythms and sensory processing in a state dependent manner. Disruptions in TRN circuitry also figures prominently in several neurodevelopmental disorders including epilepsy, autism, and attentional defects. An understanding of how and when connections between TRN and 1st order thalamic nuclei, such as the dorsal lateral geniculate nucleus (dLGN), develop is lacking. We used the mouse visual thalamus as a model system to study the organization, pattern of innervation and functional responses between TRN and the dLGN. Genetically modified mouse lines were used to visualize and target the feedforward and feedback components of these intra-thalamic circuits and to understand how peripheral input from the retina impacts their development. Retrograde tracing of thalamocortical (TC) afferents through TRN revealed that the modality-specific organization seen in the adult, is present at perinatal ages and seems impervious to the loss of peripheral input. To examine the formation and functional maturation of intrathalamic circuits between the visual sector of TRN and dLGN, we examined when projections from each nuclei arrive, and used an acute thalamic slice preparation along with optogenetic stimulation to assess the maturation of functional synaptic responses. Although thalamocortical projections passed through TRN at birth, feedforward axon collaterals determined by vGluT2 labeling, emerged during the second postnatal week, increasing in density through the third week. Optogenetic stimulation of TC axon collaterals in TRN showed infrequent, weak excitatory responses near the end of week 1. During weeks 2–4, responses became more prevalent, grew larger in amplitude and exhibited synaptic depression during repetitive stimulation. Feedback projections from visual TRN to dLGN began to innervate dLGN as early as postnatal day 2 with weak inhibitory responses emerging during week 1. During week 2–4, inhibitory responses continued to grow larger, showing synaptic depression during repetitive stimulation. During this time TRN inhibition started to suppress TC spiking, having its greatest impact by week 4–6. Using a mutant mouse that lacks retinofugal projections revealed that the absence of retinal input led to an acceleration of TRN innervation of dLGN but had little impact on the development of feedforward projections from dLGN to TRN. Together, these experiments reveal how and when intrathalamic connections emerge during early postnatal ages and provide foundational knowledge to understand the development of thalamocortical network dynamics as well as neurodevelopmental diseases that involve TRN circuitry. [ABSTRACT FROM AUTHOR]

The optic afferent nervous system (OANS) plays a significant role in generating vision and circadian behaviors based on light detection and signals from the endocrine system. However, the bionic simulation of this photochemically mediated behavior is still a challenge for neuromorphic devices. Herein, stimuli of neurotransmitters at ultralow concentrations and illumination are coupled to artificial synapses with the aid of biofunctionalized heterojunction and tunneling to successfully simulate a circadian neural response. Furthermore, the mechanisms underlying the photosensitive synaptic current in response to stimuli are described. Interestingly, this OANS is demonstrated to be capable of mimicking normal and abnormal circadian learnability by combining the measured synaptic current with a three‐layer spike neural network. Strong theoretical and experimental evidence, as well as applications, are provided for the proposed biomimetic OANS to demonstrate that it can reproduce biological circadian behavior, thus establishing it as a promising candidate for future neuromorphic intelligent robots. [ABSTRACT FROM AUTHOR]

Objective: Phenylethanolamine N‐methyltransferase (PNMT)‐expressing neurons in the nucleus tractus solitarii (NTS) contribute to the regulation of autonomic functions. However, the neural circuits linking these neurons to other brain regions remain unclear. This study aims to investigate the connectivity mechanisms of the PNMT‐expressing neurons in the NTS (NTSPNMT neurons). Methods: The methodologies employed in this study included a modified rabies virus‐based retrograde neural tracing technique, conventional viral anterograde tracing, and immunohistochemical staining procedures. Results: A total of 43 upstream nuclei projecting to NTSPNMT neurons were identified, spanning several key brain regions including the medulla oblongata, pons, midbrain, cerebellum, diencephalon, and telencephalon. Notably, dense projections to the NTSPNMT neurons were observed from the central amygdaloid nucleus, paraventricular nucleus of the hypothalamus, area postrema, and the gigantocellular reticular nucleus. In contrast, the ventrolateral medulla, lateral parabrachial nucleus, and lateral hypothalamic area were identified as the primary destinations for axon terminals originating from NTSPNMT neurons. Additionally, reciprocal projections were evident among 21 nuclei, primarily situated within the medulla oblongata. Conclusion: Our research findings demonstrate that NTSPNMT neurons form extensive connections with numerous nuclei, emphasizing their essential role in the homeostatic regulation of vital autonomic functions. [ABSTRACT FROM AUTHOR]

The article titled "Elegy for Neural Coding in Understanding Cognition: Brains are Not Computers" challenges the prevailing belief that the brain functions like a computer. The author argues that the metaphor of neural coding, which divorces the brain from its causal structure, is problematic and does not adequately explain cognitive events, thinking, and memory. The article highlights the complexity and randomness of neural processes and emphasizes that human behavior cannot be explained solely through information processing. The author suggests that researchers should move away from the information processing metaphor and focus on observing and measuring phenomena instead. [Extracted from the article]

Our brain constantly integrates afferent information, such as visual and tactile information, to perceive the world around us. According to the maximumlikelihood estimation (MLE) model, imprecise information will be weighted less than precise, making the multisensory percept as precise as possible. Individuals with fibromyalgia (FM), a chronic pain syndrome, show alterations in the integration of tactile information. This could lead to a decrease in their weight in a multisensory percept or a general disruption of multisensory integration, making it less beneficial. To assess multisensory integration, 15 participants with FM and 18 pain-free controls performed a temporal-order judgment task in which they received pairs of sequential visual, tactile (unisensory conditions), or visuotactile (multisensory condition) stimulations on the index and the thumb of the non-dominant hand and had to determine which finger was stimulated first. The task enabled us to measure the precision and accuracy of the percept in each condition. Results indicate an increase in precision in the visuotactile condition compared to the unimodal conditions in controls only, although we found no intergroup differences. The observed visuotactile precision was correlated to the precision predicted by the MLE model in both groups, suggesting an optimal integration. Finally, the weights of the sensory information were not different between the groups; however, in the group with FM, higher pain intensity was associated with smaller tactile weight. This study shows no alterations of the visuotactile integration in individuals with FM, though pain may influence tactile weight in these participants. [ABSTRACT FROM AUTHOR]

Introduction: Hox genes govern rostro-caudal identity along the developing spinal cord, which has a well-defined division of function between dorsal (sensory) and ventral (motor) halves. Here we exploit developmental Hoxb8 expression, normally restricted to the dorsal cord below the obex, to genetically label spinal cord-to-brain ("spinofugal") axons. Methods: We crossed two targeted (knock-in) and two non-targeted recombinase-expressing lines (Hoxb8-IRES-Cre and Hoxb8-T2AFlpO; Hoxb8- Cre and Hoxb8-FlpO, respectively) with appropriate tdtomato-expressing reporter strains. Serial sectioning, confocal and superresolution microscopy, as well as light-sheet imaging was used to reveal robust labeling of ascending axons and their terminals in expected and unexpected regions. Results: This strategy provides unprecedented anatomical detail of ascending spinal tracts anterior to the brainstem, and reveals a previously undescribed decussating tract in the ventral hypothalamus (the spinofugal hypothalamic decussating tract, or shxt). The absence of Hoxb8-suppressing elements led to multiple instances of ectopic reporter expression in Hoxb8-Cre mice (retinal ganglion and vomeronasal axons, anterior thalamic nuclei and their projections to the anterior cingulate and retrosplenial cortices and subiculum, and a population of astrocytes at the cephalic flexure) and Hoxb8-FlpO mice (Cajal--Retzius cells of the dentate gyrus, and mesenchymal cells of the choroid plexus). While targeted transgenic lines were similar in terms of known spinofugal projections, Hoxb8- IRES-Cre reporters had an additional projection to the core of the facial motor nucleus, and more abundant Hoxb8-lineage microglia scattered throughout the brain than Hoxb8-T2A-FlpO (or any other) mice, suggesting dysregulated Hoxb8- driven reporter expression in one or both lines. Discussion: This work complements structural and connectivity atlases of the mouse central nervous system, and provides a platform upon which their reactions to injury or disease can be studied. Ectopic Hoxb8-driven recombinase expression may also be a useful tool to study structure and function of other cell populations in non-targeted lines. [ABSTRACT FROM AUTHOR]

We report the reliable detection of reproducible patterns of blood-oxygenation-level-dependent (BOLD) MRI signals within the white matter (WM) of the spinal cord during a task and in a resting state. Previous functional MRI studies have shown that BOLD signals are robustly detectable not only in gray matter (GM) in the brain but also in cerebral WM as well as the GM within the spinal cord, but similar signals in WM of the spinal cord have been overlooked. In this study, we detected BOLD signals in the WM of the spinal cord in squirrel monkeys and studied their relationships with the locations and functions of ascending and descending WM tracts. Tactile sensory stimulus -evoked BOLD signal changes were detected in the ascending tracts of the spinal cord using a general-linear model. Power spectral analysis confirmed that the amplitude at the fundamental frequency of the response to a periodic stimulus was significantly higher in the ascending tracts than the descending ones. Independent component analysis of resting-state signals identified coherent fluctuations from eight WM hubs which correspond closely to the known anatomical locations of the major WM tracts. Resting-state analyses showed that the WM hubs exhibited correlated signal fluctuations across spinal cord segments in reproducible patterns that correspond well with the known neurobiological functions of WM tracts in the spinal cord. Overall, these findings provide evidence of a functional organization of intraspinal WM tracts and confirm that they produce hemodynamic responses similar to GM both at baseline and under stimulus conditions. [ABSTRACT FROM AUTHOR]

The present study examined the effects of transcutaneous auricular vagus nerve stimulation (taVNS) on short-latency afferent inhibition (SAI), as indirect biomarker of cholinergic system activation. 24 healthy adults underwent intermittent taVNS (30 s on/30 s off, 30 min) or continuous taVNS at a frequency of 25 Hz (15 min) along with earlobe temporary stimulation (15 min or 30 min) were performed in random order. The efficiency with which the motor evoked potential from the abductor pollicis brevis muscle by transcranial magnetic stimulation was attenuated by the preceding median nerve conditioning stimulus was compared before taVNS, immediately after taVNS, and 15 min after taVNS. Continuous taVNS significantly increased SAI at 15 min post-stimulation compared to baseline. A positive correlation (Pearson coefficient = 0.563, p = 0.004) was observed between baseline SAI and changes after continuous taVNS. These results suggest that 15 min of continuous taVNS increases the activity of the cholinergic nervous system, as evidenced by the increase in SAI. In particular, the increase after taVNS was more pronounced in those with lower initial SAI. This study provides fundamental insight into the clinical potential of taVNS for cholinergic dysfunction. [ABSTRACT FROM AUTHOR]

Afferent loop syndrome (ALS) is a rare complication of gastrectomies and gastrointestinal reconstruction. This can predispose patients to fatal conditions, such as cholangitis, pancreatitis, and duodenal perforation with peritonitis. Therefore, emergency decompression is necessary to prevent these complications. Herein, we report two cases in which transcholecystic duodenal drainage, an alternative decompression treatment, was performed in ALS patients without bile duct dilatation. Two patients who underwent distal gastrectomy with Billroth II anastomosis sought consultation in an emergency department for epigastric pain and vomiting. On CT, ALS with acute pancreatitis was diagnosed. However, biliary access could not be achieved because of the absence of bile duct dilatation. To overcome this problem, a duodenal drainage catheter was placed to decompress the afferent loop after traversing the cystic duct via a transcholecystic approach. The patients were discharged without additional surgical treatment 2 weeks and 1 month after drainage. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is characterized by a loss of neurons in the cortex and subcortical regions. Previously, we showed that the progressive degeneration of subcortical monoaminergic (MAergic) neurons seen in human AD is recapitulated in the APPswe/PS1ΔE9 (APP/PS) transgenic mouse model. Because degeneration of cholinergic (Ach) neurons is also a prominent feature of AD, we examined the integrity of the Ach system in the APP/PS model. The overall density of Ach fibers is reduced in APP/PS1 mice at 12 and 18 months of age but not at 4 months of age. Analysis of basal forebrain Ach neurons shows no loss of Ach neurons in the APP/PS model. Thus, since MAergic systems show overt cell loss at 18 months of age, the Ach system is less vulnerable to neurodegeneration in the APP/PS1 model. We also examined whether the proximity to Aβ deposition affected the degeneration of Ach and 5-HT afferents. We found that the areas closer to the edges of compact Aβ deposits exhibit a more severe loss of afferents than the areas that are more distal to Aβ deposits. Collectively, the results indicate that the APP/PS model recapitulates the degeneration of multiple subcortical neurotransmitter systems, including the Ach system. In addition, the results indicate that Aβ deposits cause global as well as local toxicity to subcortical afferents. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Afferent loop syndrome is a rare post‐operative complication following upper gastrointestinal bypass surgeries, usually occurring within the first two weeks post‐operation. This case report, however, outlines afferent loop syndrome almost a decade post‐surgery, which was managed conservatively. A 54‐year‐old woman presented with a few days' history of epigastric pain, vomiting, and constipation. She had undergone a sleeve gastrectomy and was converted to a Roux‐en‐Y gastrojejunostomy for weight loss 9 and 7 years ago, respectively. Serum lipase was elevated at 1410 IU/L. Computed tomography showed high‐grade proximal small bowel obstruction, involving the efferent and afferent loops of the Roux‐en‐Y gastric bypass. The patient was given intravenous rehydration, electrolyte replacement and had a nasogastric tube inserted. She was discharged on day 5 of admission without significant sequelae. Afferent limb syndrome should be considered in patients with altered upper gastrointestinal anatomy who present with pancreatitis, regardless of the time period post‐operatively. Future guidelines should further more outline the factors indicated for surgical versus conservative management. [ABSTRACT FROM AUTHOR]

Purpose: Pudendal neuropathy is an uncommon condition that exhibits several symptoms depending on the site of nerve entrapment. This study aims to evaluate the efficacy of pudendal nerve neurolysis (PNN) in improving lower urinary tract symptoms, anal and/or urinary incontinence, and sexual dysfunctions. Materials and Methods: A systematic literature search was performed on 20 May 2023 using Scopus, PubMed, and Embase. Only English and adult papers were included. Meeting abstracts and preclinical studies were excluded. Results: Twenty-one papers were accepted, revealing significant findings in the field. The study identified four primary sites of pudendal nerve entrapment (PNE), with the most prevalent location likely being at the level of the Alcock canal. Voiding symptoms are commonly exhibited in patients with PNE. PNN improved both urgency and voiding symptoms, and urinary and anal incontinence but is less effective in cases of long-standing entrapment. Regarding sexual function, the recovery of the somatic afferent pathway results in an improvement in erectile function early after neurolysis. Complete relief of persistent genital arousal disorder occurs in women, although bilateral PNN is necessary to achieve the efficacy. PNN is associated with low-grade complications. Conclusions: PNN emerges as a viable option for addressing urinary symptoms, fecal incontinence, erectile dysfunction, and female sexual arousal in patients suffering from PNE with minimal postoperative morbidity. [ABSTRACT FROM AUTHOR]

This article discusses the reliability and learning effect of sit-to-stand tests in assessing lower limb strength in adults and older adults. The study found that the 1-minute sit-to-stand test (1MSTS) and the 5 times sit-to-stand test (5TSTS) showed excellent within-day test-retest reliability in both age groups. However, there was a learning effect observed in adults, but not in older adults. The findings suggest that at least three tests are needed for adults to achieve their true performance, while a single test may be sufficient for older adults. Further research is needed to explore the influence of other variables on the reliability and learning effect of these tests. [Extracted from the article]

Background: Charcot–Marie–Tooth disease (CMT) is a heterogeneous group of disorders involving peripheral nervous system. Charcot–Marie–Tooth disease 4B1 (CMT4B1) is a rare subtype of CMT. CMT4B1 is an axonal demyelinating polyneuropathy with an autosomal recessive mode of inheritance. Patients with CMT4B1 usually manifested with dysfunction of the motor and sensory systems which leads to gradual and progressive muscular weakness and atrophy, starting from the peroneal muscles and finally affecting the distal muscles. Germline mutations in MTMR2 gene causes CMT4B1. Material and Methods: In this study, we investigated a 4-year-old Chinese boy with gradual and progressive weakness and atrophy of both proximal and distal muscles. The proband's parents did not show any abnormalities. Whole-exome sequencing and Sanger sequencing were performed. Results: Whole-exome sequencing identified a novel homozygous nonsense mutation (c.118A>T; p.Lys40*) in exon 2 of MTMR2 gene in the proband. This novel mutation leads to the formation of a truncated MTMR2 protein of 39 amino acids instead of the wild- type MTMR2 protein of 643 amino acids. This mutation is predicted to cause the complete loss of the PH-GRAM domain, phosphatase domain, coiled-coil domain, and PDZ-binding motif of the MTMR2 protein. Sanger sequencing revealed that the proband's parents carried the mutation in a heterozygous state. This mutation was absent in 100 healthy control individuals. Conclusion: This study reports the first mutation in MTMR2 associated with CMT4B1 in a Chinese population. Our study also showed the importance of whole-exome sequencing in identifying candidate genes and disease-causing variants in patients with CMT4B1. [ABSTRACT FROM AUTHOR]

Amniotes feature two principal visual processing systems: the tectofugal and thalamofugal pathways. In most mammals, the thalamofugal pathway predominates, routing retinal afferents through the dorsolateral geniculate complex to the visual cortex. In most birds, the thalamofugal pathway often plays the lesser role with retinal afferents projecting to the principal optic thalami, a complex of several nuclei that resides in the dorsal thalamus. This thalamic complex sends projections to a forebrain structure called the Wulst, the terminus of the thalamofugal visual system. The thalamofugal pathway in birds serves many functions such as pattern discrimination, spatial memory, and navigation/migration. A comprehensive analysis of avian species has unveiled diverse subdivisions within the thalamic and forebrain structures, contingent on species, age, and techniques utilized. In this study, we documented the thalamofugal system in three dimensions by integrating histological and contrast-enhanced computed tomography imaging of the avian brain. Sections of two-week-old chick brains were cut in either coronal, sagittal, or horizontal planes and stained with Nissl and either Gallyas silver or Luxol Fast Blue. The thalamic principal optic complex and pallial Wulst were subdivided on the basis of cell and fiber density. Additionally, we utilized the technique of diffusible iodine-based contrast-enhanced computed tomography (diceCT) on a 5-week-old chick brain, and right eyeball. By merging diceCT data, stained histological sections, and information from the existing literature, a comprehensive three-dimensional model of the avian thalamofugal pathway was constructed. The use of a 3D model provides a clearer understanding of the structural and spatial organization of the thalamofugal system. The ability to integrate histochemical sections with diceCT 3D modeling is critical to better understanding the anatomical and physiologic organization of complex pathways such as the thalamofugal visual system. [ABSTRACT FROM AUTHOR]

This article discusses the potential of Stathmin 2 (STMN2) as a treatment target for TDP-43 proteinopathy in amyotrophic lateral sclerosis (ALS). TDP-43 is a protein associated with ALS, and its abnormal modifications lead to neurotoxic effects. The study found that the expression of STMN2 was significantly reduced in the presence of TDP-43 depletion, and restoring STMN2 levels rescued neurite outgrowth and axon regeneration. The article suggests that STMN2 is involved in ALS pathology and could be a promising therapeutic approach. However, further research and in vivo examination are needed to confirm the efficacy and safety of targeting STMN2. [Extracted from the article]

Human cingulate sulcus visual area (CSv) was first identified as an area that responds selectively to visual stimulation indicative of self-motion. It was later shown that the area is also sensitive to vestibular stimulation as well as to bodily motion compatible with locomotion. Understanding the anatomical connections of CSv will shed light on how CSv interacts with other parts of the brain to perform information processing related to self-motion and navigation. A previous neuroimaging study (Smith et al. 2018, Cerebral Cortex, 28, 3685–3596) used diffusion-weighted magnetic resonance imaging (dMRI) to examine the structural connectivity of CSv, and demonstrated connections between CSv and the motor and sensorimotor areas in the anterior and posterior cingulate sulcus. The present study aimed to complement this work by investigating the relationship between CSv and adjacent major white matter tracts, and to map CSv's structural connectivity onto known white matter tracts. By re-analysing the dataset from Smith et al. (2018), we identified bundles of fibres (i.e. streamlines) from the whole-brain tractography that terminate near CSv. We then assessed to which white matter tracts those streamlines may belong based on previously established anatomical prescriptions. We found that a significant number of CSv streamlines can be categorised as part of the dorsalmost branch of the superior longitudinal fasciculus (SLF I) and the cingulum. Given current thinking about the functions of these white matter tracts, our results support the proposition that CSv provides an interface between sensory and motor systems in the context of self-motion. [ABSTRACT FROM AUTHOR]

Hindlimb ischaemia–reperfusion (IR) is among the most prominent pathophysiological conditions observed in peripheral artery disease (PAD). An exaggerated arterial blood pressure (BP) response during exercise is associated with an elevated risk of cardiovascular events in individuals with PAD. However, the precise mechanisms leading to this exaggerated BP response are poorly elucidated. The P2X3 signalling pathway, which plays a key role in modifying the exercise pressor reflex (EPR), is the focus of the present study. We determined the regulatory role of P2X3 on the EPR in a rat model of hindlimb IR. In vivo and in vitro approaches were used to determine the expression and functions of P2X3 in muscle afferent nerves and EPR in IR rats. We found that in IR rats there was (1) upregulation of P2X3 protein expression in the L4–6 dorsal root ganglia (DRG); (2) amplified P2X currents in isolated isolectin B4 (IB4)‐positive muscle DRG neurons; and (3) amplification of the P2X‐mediated BP response. We further verified that both A‐317491 and siRNA knockdown of P2X3 significantly decreased the activity of P2X currents in isolated muscle DRG neurons. Moreover, inhibition of muscle afferents' P2X3 receptor using A‐317491 was observed to alleviate the exaggerated BP response induced by static muscle contraction and P2X‐induced BP response by α,β‐methylene ATP injection. P2X3 signalling pathway activity is amplified in muscle afferent DRG neurons in regulating the EPR following hindlimb IR. What is the central question of this study?Is the P2X3 signal pathway engaged in the exaggerated exercise pressor reflex (EPR) response in the ischaemia–reperfusion (IR) injury of peripheral artery disease (PAD)?What is the main finding and its importance?IR upregulates expression of the P2X3 receptor and increases the P2X currents in muscle afferent DRG neurons. Pharmacological inhibition using A‐317491 (P2X3 antagonist) and the genetic knockdown of P2X3 reduce the P2X currents in the muscle afferent DRG neurons. A‐317491 also attenuates the exacerbated EPR response following IR.The findings provide evidence that interventions attenuating the P2X3 signalling pathway may enhance tolerance of and adherence to exercise rehabilitation for PAD patients. [ABSTRACT FROM AUTHOR]

We recently used Nav1.8-ChR2 mice in which Nav1.8-expressing afferents were optogenetically tagged to classify mechanosensitive afferents into Nav1.8-ChR2-positive and Nav1.8-ChR2-negative mechanoreceptors. We found that the former were mainly high threshold mechanoreceptors (HTMRs), while the latter were low threshold mechanoreceptors (LTMRs). In the present study, we further investigated whether the properties of these mechanoreceptors were altered following tissue inflammation. Nav1.8-ChR2 mice received a subcutaneous injection of saline or Complete Freund's Adjuvant (CFA) in the hindpaws. Using the hind paw glabrous skin-tibial nerve preparation and the pressure-clamped single-fiber recordings, we found that CFA-induced hind paw inflammation lowered the mechanical threshold of many Nav1.8-ChR2-positive Aβ-fiber mechanoreceptors but heightened the mechanical threshold of many Nav1.8-ChR2-negative Aβ-fiber mechanoreceptors. Spontaneous action potential impulses were not observed in Nav1.8-ChR2-positive Aβ-fiber mechanoreceptors but occurred in Nav1.8-ChR2-negative Aβ-fiber mechanoreceptors with a lower mechanical threshold in the saline goup, and a higher mechanical threshold in the CFA group. No significant change was observed in the mechanical sensitivity of Nav1.8-ChR2-positive and Nav1.8-ChR2-negative Aδ-fiber mechanoreceptors and Nav1.8-ChR2-positive C-fiber mechanoreceptors following hind paw inflammation. Collectively, inflammation significantly altered the functional properties of both Nav1.8-ChR2-positive and Nav1.8-ChR2-negative Aβ-fiber mechanoreceptors, which may contribute to mechanical allodynia during inflammation. [ABSTRACT FROM AUTHOR]

Diabetic neuropathy is the most common complication of diabetes and lacks effective treatments. Although sensory dysfunction during the early stages of diabetes has been extensively studied in various animal models, the functional and morphological alterations in sensory and motor systems during late stages of diabetes remain largely unexplored. In the current work, we examined the influence of diabetes on sensory and motor function as well as morphological changes in late stages of diabetes. The obese diabetic Leprdb/db mice (db/db) were used for behavioral assessments and subsequent morphological examinations. The db/db mice exhibited severe sensory and motor behavioral defects at the age of 32 weeks, including significantly higher mechanical withdrawal threshold and thermal latency of hindpaws compared with agematched nondiabetic control animals. The impaired response to noxious stimuli was mainly associated with the remarkable loss of epidermal sensory fibers, particularly CGRP-positive nociceptive fibers. Unexpectedly, the area of CGRPpositive terminals in the spinal dorsal horn was dramatically increased in diabetic mice, which was presumably associated with microglial activation. In addition, the db/db mice showed significantly more foot slips and took longer time during the beam-walking examination compared with controls. Meanwhile, the running duration in the rotarod test was markedly reduced in db/db mice. The observed sensorimotor deficits and motor dysfunction were largely attributed to abnormal sensory feedback and muscle atrophy as well as attenuated neuromuscular transmission in aged diabetic mice. Morphological analysis of neuromuscular junctions (NMJs) demonstrated partial denervation of NMJs and obvious fragmentation of acetylcholine receptors (AChRs). Intrafusal muscle atrophy and abnormal muscle spindle innervation were also detected in db/db mice. Additionally, the number of VGLUT1-positive excitatory boutons on motor neurons was profoundly increased in aged diabetic mice as compared to controls. Nevertheless, inhibitory synaptic inputs onto motor neurons were similar between the two groups. This excitation-inhibition imbalance in synaptic transmission might be implicated in the disturbed locomotion. Collectively, these results suggest that severe sensory and motor deficits are present in late stages of diabetes. This study contributes to our understanding of mechanisms underlying neurological dysfunction during diabetes progression and helps to identify novel therapeutic interventions for patients with diabetic neuropathy. [ABSTRACT FROM AUTHOR]

The entorhinal cortex is involved in establishing enduring visuo-auditory associative memory in the neocortex. Here we explored the mechanisms underlying this synaptic plasticity related to projections from the visual and entorhinal cortices to the auditory cortex in mice using optogenetics of dual pathways. High-frequency laser stimulation (HFS laser) of the visuo-auditory projection did not induce long-term potentiation. However, after pairing with sound stimulus, the visuo-auditory inputs were potentiated following either infusion of cholecystokinin (CCK) or HFS laser of the entorhino-auditory CCK-expressing projection. Combining retrograde tracing and RNAscope in situ hybridization, we show that Cck expression is higher in entorhinal cortex neurons projecting to the auditory cortex than in those originating from the visual cortex. In the presence of CCK, potentiation in the neocortex occurred when the presynaptic input arrived 200 ms before postsynaptic firing, even after just five trials of pairing. Behaviorally, inactivation of the CCK+ projection from the entorhinal cortex to the auditory cortex blocked the formation of visuo-auditory associative memory. Our results indicate that neocortical visuo-auditory association is formed through heterosynaptic plasticity, which depends on release of CCK in the neocortex mostly from entorhinal afferents. [ABSTRACT FROM AUTHOR]

Innate defensive responses, though primarily instinctive, must also be highly adaptive to changes in risk assessment. However, adaptive changes can become maladaptive, following severe stress, as seen in posttraumatic stress disorder (PTSD). In a series of experiments, we observed long-term changes in innate escape behavior of male mice towards a previously non-threatening stimulus following an adverse shock experience manifested as a shift in the threshold of threat response. By recording neural activity in the superior colliculus (SC) while phototagging specific responses to afferents, we established the crucial influence of input arriving at the SC from the medial prefrontal cortex (mPFC), both directly and indirectly, on escape-related activity after adverse shock experience. Inactivating these specific projections during the shock effectively abolished the observed changes. Conversely, optogenetically activating them during encounters controlled escape responses. This establishes the necessity and sufficiency of those specific mPFC inputs into the SC for adverse experience related changes in innate escape behavior. Significant aversive experience can cause lasting behavioral changes due to shifts in arousal thresholds and filter mechanisms. Here, in male mice, the authors identify a change in a neural circuit, underlying adversity driven enhanced threat response. [ABSTRACT FROM AUTHOR]

Intravenous (systemic) bolus injection of fentanyl (FNT) reportedly induces an immediate vagal-mediated apnea; however, the precise origin of vagal afferents responsible for this apnea remains unknown. We tested whether intralaryngeal (local) application of FNT would also trigger an apnea and whether the apneic response to both local and systemic administration of FNT was laryngeal afferentmediated. Cardiorespiratory responses to FNT were recorded in anesthetized male adult rats with and without bilateral sectioning of the superior laryngeal nerve (SLNx) or peri-SLN capsaicin treatment (SLNcap) to block local C-fiber signal conduction. Opioid mu-receptor (MOR)-immunoreactivity was detected in laryngeal C- and myelinated neurons. We found that local and systemic administration of FNT elicited an immediate apnea. SLNx, rather than SLNcap, abolished the apneic response to local FNT application though MORs were abundantly expressed in both laryngeal C- and myelinated neurons. Importantly, SLNx failed to affect the apneic response to systemic FNT administration. These results lead to the conclusion that laryngeal afferents' MORs are responsible for the apneic response to local, but not systemic, administration of FNT. [ABSTRACT FROM AUTHOR]

In mammalian hearing, type-I afferent auditory nerve fibers comprise the basis of the afferent auditory pathway. They are connected to inner hair cells of the cochlea via specialized ribbon synapses. Auditory nerve fibers of different physiological types differ subtly in their synaptic location and morphology. Low-spontaneous-rate auditory nerve fibers typically connect on the modiolar side of the inner hair cell, while high-spontaneous-rate fibers are typically found on the pillar side. In aging and noise-damaged ears, this fine-tuned balance between auditory nerve fiber populations can be disrupted and the functional consequences are currently unclear. Here, using immunofluorescent labeling of presynaptic ribbons and postsynaptic glutamate receptor patches, we investigated changes in synaptic morphology at three different tonotopic locations along the cochlea of aging gerbils compared to those of young adults. Quiet-aged gerbils showed about 20% loss of afferent ribbon synapses. While the loss was random at apical, low-frequency cochlear locations, at the basal, high-frequency location it almost exclusively affected the modiolar-located synapses. The subtle differences in volumes of pre- and postsynaptic elements located on the inner hair cell's modiolar versus pillar side were unaffected by age. This is consistent with known physiology and suggests a predominant, age-related loss in the low-spontaneous-rate auditory nerve population in the cochlear base, but not the apex. [ABSTRACT FROM AUTHOR]

Introduction: Severe spinal cord injury results in the loss of neurons in the relatively intact spinal cord below the injury area and skeletal muscle atrophy in the paralyzed limbs. These pathological processes are significant obstacles for motor function reconstruction. Objective: We performed tail nerve electrical stimulation (TNES) to activate the motor neural circuits below the injury site of the spinal cord to elucidate the regulatory mechanisms of the excitatory afferent neurons in promoting the reconstruction of locomotor function. Methods: Eight days after T10 spinal cord transection in rats, TNES was performed for 7 weeks. Behavioral scores were assessed weekly. Electrophysiological tests and double retrograde tracings were performed at week 8. Results: After 7 weeks of TNES treatment, there was restoration in innervation, the number of stem cells, and mitochondrial metabolism in the rats' hindlimb muscles. Double retrograde tracings of the tail nerve and sciatic nerve further confirmed the presence of synaptic connections between the tail nerve and central pattern generator (CPG) neurons in the lumbar spinal cord, as well as motor neurons innervating the hindlimb muscles. Conclusion: The mechanisms of TNES induced by the stimulation of primary afferent nerve fibers involves efficient activation of the motor neural circuits in the lumbosacral segment, alterations of synaptic plasticity, and the improvement of muscle and nerve regeneration, which provides the structural and functional foundation for the future use of cutting‐edge biological treatment strategies to restore voluntary movement of paralyzed hindlimbs. [ABSTRACT FROM AUTHOR]

This article presents a study on the brainstem auditory-evoked potential (BAEP) in patients with vertebrobasilar transient ischemic attack (VBTIA). The study found that VBTIA patients had a prolonged absolute latency of wave V and a reduction in amplitude of wave V, which was statistically significant. These findings suggest that BAEP could be a useful tool for early detection of stroke progression in VBTIA patients. However, further research is needed to better understand the relationship between electrophysiological parameters and stroke progression. [Extracted from the article]

"The Routledge International Handbook of Research on Writing" by R. Horowitz is a comprehensive handbook that explores various aspects of writing. The book covers topics such as the history of writing, the connection between speaking and writing, cognitive processes in writing, and the use of digital tools for writing. The reviewer praises the overall quality of the handbook and highlights specific chapters on digital writing, intercultural rhetoric research, everyday writing, and writing in the sciences and engineering. The reviewer suggests that future editions could include additional chapters on text quality assessment, research methods in writing research, and the future of writing in the age of AI. [Extracted from the article]

Early-life environmental signals contribute to how the brain handles reward, stress, and fear.

Background: Transcutaneous auricular vagus nerve stimulation (taVNS) is considered a safe and promising tool for limb rehabilitation after stroke, but its effect on cough has never been studied. It is known that the ear and larynx share vagal afferent pathways, suggesting that stimulating the ear with taVNS might have effects on cough sensitivity. The specific stimulation parameters used can influence outcomes. Objective: To investigate the effect of various stimulation parameters on change in cough sensitivity, compared to the reference parameter of 25 Hz stimulation at the left concha (most commonly-used parameter for stroke rehabilitation). Design, setting, and participants: Randomized, single-blind, active-controlled, eight-period cross-over design conducted March to August 2022 at a New Zealand research laboratory with 16 healthy participants. Interventions: All participants underwent eight stimulation conditions which varied by stimulation side (right ear, left ear), zone (ear canal, concha), and frequency (25 Hz, 80 Hz). Main outcome measures: Change in natural and suppressed cough threshold (from baseline to after 10 min of stimulation) assessed using a citric acid cough reflex test. Results: When compared to the reference parameter of 25 Hz stimulation at the left concha, there was a reduction in natural cough threshold of -0.16 mol/L for 80 Hz stimulation at the left canal (p = 0.004), indicating increased sensitivity. For the outcome measure of suppressed cough threshold, there was no significant effect of any of the stimulation conditions compared to the active reference. Conclusion: Since stroke patients often have cough hyposensitivity with resulting high risk of silent aspiration, using 80 Hz taVNS at the left canal may be a better choice for future stroke rehabilitation studies than the commonly used 25 Hz taVNS at the left concha. Treatment parameters should be manipulated in future sham-controlled trials to maximize any potential treatment effect of taVNS in modulating cough sensitivity. [ABSTRACT FROM AUTHOR]

Background: Vagal afferent neurons represent the key neurosensory branch of the gut-brain axis, which describes the bidirectional communication between the gastrointestinal system and the brain. These neurons are important for detecting and relaying sensory information from the periphery to the central nervous system to modulate feeding behavior, metabolism, and inflammation. Confounding variables complicate the process of isolating the role of the vagal afferents in mediating these physiological processes. Therefore, we developed a microfluidic model of the sensory branch of the gut-brain axis. We show that this microfluidic model successfully compartmentalizes the cell body and neurite terminals of the neurons, thereby simulates the anatomical layout of these neurons to more accurately study physiologically-relevant processes. Methods: We implemented a primary rat vagal afferent neuron culture into a microfluidic platform consisting of two concentric chambers interconnected with radial microchannels. The microfluidic platform separated cell bodies from neurite terminals of vagal afferent neurons. We then introduced physiologically-relevant gastrointestinal effector molecules at the nerve terminals and assessed their retrograde transport along the neurite or capacity to elicit an electrophysiological response using live cell calcium imaging. Results: The angle of microchannel outlets dictated the probability of neurites growing into a chamber versus tracking along chamber walls. When the neurite terminals were exposed to fluorescently-labeled cholera toxin subunit B, the proteins were taken up and retrogradely transported along the neurites over the course of 24 h. Additionally, mechanical perturbation (e.g., rinsing) of the neurite terminals significantly increased intracellular calcium concentration in the distal soma. Finally, membrane-displayed receptor for capsaicin was expressed and trafficked along newly projected neurites, as revealed by confocal microscopy. Conclusions: In this work, we developed a microfluidic device that can recapitulate the anatomical layout of vagal afferent neurons in vitro. We demonstrated two physiologically-relevant applications of the platforms: retrograde transport and electrophysiological response. We expect this tool to enable controlled studies on the role of vagal afferent neurons in the gut-brain axis. [ABSTRACT FROM AUTHOR]

In the past few decades, the use of acupuncture analgesia in clinical practice has increased worldwide. This is due to its various benefits, including natural alleviation of pain without causing various adverse effects associated with nonsteroidal anti-inflammatory drugs (NSAID) and opioids. The acupoint represents the initial site of acupuncture stimulation, where diverse types of nerve fibers located at the acupoint hold significant roles in the generation and transmission of acupuncture-related information. In this study, we analyzed the patterns and mechanisms of acupuncture analgesic mediated by acupoint afferent fibers, and found that acupuncture stimulates acupoints which rapidly and directly induces activation of high-density primary afferent fibers under the acupoints, including myelinated A fibers and unmyelinated C fibers. During acupuncture stimulation at the muscle layer, the analgesic effects can be induced by stimulation of A fiber threshold intensity. At the skin layer, the analgesic effects can only be produced by stimulation of C fiber threshold intensity. Electroacupuncture (EA) activates A fibers, while manual acupuncture (MA) activates both A and C fibers. Furthermore, acupuncture alters acupoint microenvironments, which positively modulates afferent fibers, enhancing the transmission of analgesic signals. In addition to local activation and conduction at acupoints, nerve fibers mediate the transmission of acupuncture information to pain centers. In the spinal cord, acupuncture activates neurons by inducing afferent fiber depolarization, modulating pain gating, inhibiting long-term potentiation (LTP) of the spinal dorsal horn and wide dynamic range (WDR) neuronal activities. At higher nerve centers, acupuncture inhibits neuronal activation in pain-related brain regions. In summary, acupuncture inhibits pain signal transmission at peripheral and central systems by activating different patterns of afferent fibers located on various layers of acupoints. This study provides ideas for enhancing the precise application and clinical translation of acupuncture. [ABSTRACT FROM AUTHOR]

Migraine headache is hypothesized to involve the activation and sensitization of trigeminal sensory afferents that innervate the cranial meninges. To better understand migraine pathophysiology and improve clinical translation, we used two-photon calcium imaging via a closed cranial window in awake mice to investigate changes in the responses of meningeal afferent fibers using a preclinical model of migraine involving cortical spreading depolarization (CSD). A single CSD episode caused a seconds-long wave of calcium activation that propagated across afferents and along the length of individual afferents. Surprisingly, unlike previous studies in anesthetized animals with exposed meninges, only a very small afferent population was persistently activated in our awake mouse preparation, questioning the relevance of this neuronal response to the onset of migraine pain. In contrast, we identified a larger subset of meningeal afferents that developed augmented responses to acute three-dimensional meningeal deformations that occur in response to locomotion bouts. We observed increased responsiveness in a subset of afferents that were already somewhat sensitive to meningeal deformation before CSD. Furthermore, another subset of previously insensitive afferents also became sensitive to meningeal deformation following CSD. Our data provides new insights into the mechanisms underlying migraine, including the emergence of enhanced meningeal afferent responses to movement-related meningeal deformations as a potential neural substrate underlying the worsening of migraine headache during physical activity. [ABSTRACT FROM AUTHOR]

This article describes a rare case of trigeminal neuralgia (TN) caused by compression on the trigeminal sensory nucleus and tract by an aberrant dual anastomotic artery loop. The patient, a 74-year-old male, experienced progressive episodic pain in the left forehead, eyelid, cheek, and jaw. Brain MRI revealed compression on the pons near the fourth ventricle caused by the left posterior inferior cerebellar artery (PICA) and an anastomotic loop connecting the anterior inferior cerebellar artery (AICA) and PICA. The patient underwent endoscopic-assisted microvascular decompression (MVD), which successfully relieved the pain. The article discusses the vulnerability of the trigeminal nerve to vascular forces and the effectiveness of MVD in reversing microstructural changes. It also highlights the need for further research on the mechanism and treatment of TN caused by vascular compression. [Extracted from the article]

During object manipulation, humans adjust the grip force to friction, such that slippery objects are squeezed more firmly than sticky ones. This essential mechanism to keep a stable grasp relies on feedback from tactile afferents innervating the fingertips, that are sensitive to local skin strains. To test if this feedback originates from the skin-object interface, we asked participants to perform a grip-lift task with an instrumented object able to monitor skin strains at the contact through transparent plates of different frictions. We observed that, following an unbeknown change in plate across trials, participants adapted their grip force to friction. After switching from high to low friction, we found a significant increase in strain inside the contact arising ~100 ms before the modulation of grip force, suggesting that differences in strain patterns before lift-off are used by the nervous system to quickly adjust the force to the frictional properties of manipulated objects. [ABSTRACT FROM AUTHOR]

Cartwheel interneurons of the dorsal cochlear nucleus (DCN) potently suppress multisensory signals that converge with primary auditory afferent input, and thus regulate auditory processing. Noradrenergic fibers from locus coeruleus project to the DCN, and α2-adrenergic receptors inhibit spontaneous spike activity but simultaneously enhance synaptic strength in cartwheel cells, a dual effect leading to enhanced signal-to-noise for inhibition. However, the ionic mechanism of this striking modulation is unknown. We generated a glycinergic neuron-specific knockout of the Na+ leak channel NALCN in mice and found that its presence was required for spontaneous firing in cartwheel cells. Activation of α2-adrenergic receptors inhibited both NALCN and spike generation, and this modulation was absent in the NALCN knockout. Moreover, α2-dependent enhancement of synaptic strength was also absent in the knockout. GABAB receptors mediated inhibition through NALCN as well, acting on the same population of channels as α2 receptors, suggesting close apposition of both receptor subtypes with NALCN. Thus, multiple neuromodulatory systems determine the impact of synaptic inhibition by suppressing the excitatory leak channel, NALCN. [ABSTRACT FROM AUTHOR]